I propose to study epithelial renewal in experimental and clinical peptic ulcer disease, during acute and chronic administration of potential ulcerogens, and during malignant transformation of experimental gastric ulcer after exposure to a carcinogen. The relevance of these studies is that alterations in epithelial renewal may play a role in the pathogenesis of peptic disease and the development of gastric cancer. The methods which we will use will include light microscopy, light autoradiography, and electron microscopy in both rats and humans and, in humans, organ culture of upper gastrointestinal biopsies. In rats, we will study epithelial renewal: (1) after chronic administration of ulcerogens, such as aspirin or ethanol, (2) during healing of discrete experimental gastric ulcer, (3) during malignant transformation of experimental gastric ulcer after exposure to a carcinogen, and (4) during treatment with gastrin and/or cimetidine after either acute or chronic mucosal injury. In humans, we will study epithelial renewal: (1) in patients with gastric ulcer, before and after healing, (2) in patients with duodenal ulcer, before and after healing, (3) in patients with acute gastritis of diverse etiology, and (4) in patients who chronically consume potential ulcerogens, such as aspirin, indomethacin, ethanol, and steroids.